Galectin-3 Modulates Immune and Inflammatory Responses during Helminthic Infection: Impact of Galectin-3 Deficiency on the Functions of Dendritic Cells

Breuilh, Laëtitia; Vanhoutte, François; Fontaine, Josette; Stijn, Caroline M.W. van; Tillie‐Leblond, I.; Capron, Moníque; Faveeuw, Christelle; Jouault, Thierry; Die, Irma van; Gosset, Philippe; Trottein, François

doi:10.1128/iai.02006-06

Cited by 98 publications

(81 citation statements)

References 59 publications

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“…Thus, Gal-2 and Gal-3 may be important in innate immune mechanisms in recognizing blood group-related glycans. Consistent with this, recent studies suggest a role for Gal-3 in innate immune recognition of several pathogens, including Candida albicans (69), Leishmania major (68,71) and Schistosoma mansoni (72,73). Given the relationship between galectins and the innate immunity (74), future studies will continue to examine the effect and modulation galectins impose on the innate immune system.…”

Section: Tablementioning

confidence: 65%

Galectin-1, -2, and -3 Exhibit Differential Recognition of Sialylated Glycans and Blood Group Antigens

Stowell

Arthur

Mehta

et al. 2008

Journal of Biological Chemistry

375

472

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Human galectins have functionally divergent roles, although most of the members of the galectin family bind weakly to the simple disaccharide lactose (Gal␤1-4Glc). To assess the specificity of galectin-glycan interactions in more detail, we explored the binding of several important galectins (Gal-1, Gal-2, and Gal-3) using a dose-response approach toward a glycan microarray containing hundreds of structurally diverse glycans, and we compared these results to binding determinants on cells. All three galectins exhibited differences in glycan binding characteristics. On both the microarray and on cells, Gal-2 and Gal-3 exhibited higher binding than Gal-1 to fucose-containing A and B blood group antigens. Gal-2 exhibited significantly reduced binding to all sialylated glycans, whereas Gal-1 bound ␣2-3-but not ␣2-6-sialylated glycans, and Gal-3 bound to some glycans terminating in either ␣2-3-or ␣2-6-sialic acid. The effects of sialylation on Gal-1, Gal-2, and Gal-3 binding to cells also reflected differences in cellular sensitivity to Gal-1-, Gal-2-, and Gal-3-induced phosphatidylserine exposure. Each galectin exhibited higher binding for glycans with poly-N-acetyllactosamine (poly(LacNAc)) sequences (Gal␤1-4GlcNAc) n when compared with N-acetyllactosamine (LacNAc) glycans (Gal␤1-4GlcNAc). However, only Gal-3 bound internal LacNAc within poly(LacNAc). These results demonstrate that each of these galectins mechanistically differ in their binding to glycans on the microarrays and that these differences are reflected in the determinants required for cell binding and signaling. The specific glycan recognition by each galectin underscores the basis for differences in their biological activities.

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Section: Tablementioning

confidence: 65%

Galectin-1, -2, and -3 Exhibit Differential Recognition of Sialylated Glycans and Blood Group Antigens

Stowell

Arthur

Mehta

et al. 2008

Journal of Biological Chemistry

375

472

View full text Add to dashboard Cite

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“…Neutrophil recruitment in S. pneumoniae is independent of b2 integrin whereas the b2 integrin-dependent recruitment in Escherichia Coli infection was not affected by the lack of Gal-3 (Nieminen et al 2008). Increased survival of Gal-3 null mice has been observed following intracerebral and peripheral scrapie infection (Mok et al 2007), while Gal-3 null mice have reduced granuloma formation following infection with Schistosomiasis (Breuilh et al 2007), a disease normally characterised by a Th2-driven response. Gal-3 null mice, however, mounted a biased Th1 response as demonstrated by increased IFNG and IgG2b levels.…”

Section: Galectin-3 and The In Vivo Immune Responsementioning

confidence: 95%

Endogenous galectins and the control of the host inflammatory response

Norling¹,

Perretti²,

Cooper³

2009

Journal of Endocrinology

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A new era of research is being devoted to deciphering endogenous mediators and mechanisms that are in place to resolve the inflammatory response. Accruing evidence indicates that galectins fall into this category of immunoregulatory mediators signifying their use as prospective novel anti-inflammatory agents. The focus of this review is to depict the immunoregulatory bioactivities of three members of the galectin superfamily, Galectin (Gal)-1, Gal-3 and Gal-9.Emphasis is given to the studies investigating the properties of these endogenous lectins. Gal-1, Gal-3 and Gal-9 are emerging as pertinent players in the modulation of acute and chronic inflammatory diseases, autoimmunity and cancer, and thus being increasingly recognised as molecular targets for innovative drug discovery.

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“…The role of gal3 in the modulation of Th1 and Th2 responses was reported in different disease models, including airway remodeling in asthma (9) and R. equi (7), P. brasiliensis (10), T. gondii, and Schistosoma mansoni infections (6,7,33). Gal3 suppresses Th1 (6) and Th2 (10) responses, depending on the infectious agents involved.…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

Liu

et al. 2013

The Journal of Immunology

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Galectin-3 (gal3) is known for its immunoregulatory functions in infectious, autoimmune, and inflammatory diseases. However, little is known about its regulatory role in the host's IL-17A response to infection. Using a mouse model of histoplasmosis in which both Th1 and Th17 responses contribute to fungal clearance, we investigated how gal3 regulates IL-17A responses. Our study showed that Histoplasma infection induced gal3−/− dendritic cells to produce significantly higher levels of IL-23, TGF-β1, and IL-1β than did gal3+/+ cells. Infected by the same inoculum of Histoplasma, gal3−/− mice had lower fungal burden and produced higher levels of IL-23/IL-17–axis cytokines and lower levels of IL-12 and IFN-γ. Additionally, there was an increase in Th17 cells and a reduction in Th1 cells in infected gal3−/− mice. In vitro Th1/Th17-skewing experiments excluded the intrinsic effect of gal3 on Th cell differentiation. Although neutrophils from both gal3+/+ and gal3−/− mice produced IL-17A upon IL-23 stimulation, their contribution to IL-17A production was greater in gal3−/− mice than in gal3+/+ mice. Compared with gal3+/+ dendritic cells, adoptive transfer of gal3−/− dendritic cells resulted in production of significantly higher levels of IL-17–axis cytokines and reduced fungal burden. It appears that reduced fungal burden and preferential IL-17A response in gal3−/− mice by both Th17 cells and neutrophils were the result of preferential production of IL-23/IL-17–axis cytokines by dendritic cells. Our study showed that gal3 negatively regulates IL-17A responses through inhibition of IL-23/IL-17–axis cytokine production by dendritic cells.

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Galectin-3 Modulates Immune and Inflammatory Responses during Helminthic Infection: Impact of Galectin-3 Deficiency on the Functions of Dendritic Cells

Cited by 98 publications

References 59 publications

Galectin-1, -2, and -3 Exhibit Differential Recognition of Sialylated Glycans and Blood Group Antigens

Galectin-1, -2, and -3 Exhibit Differential Recognition of Sialylated Glycans and Blood Group Antigens

Endogenous galectins and the control of the host inflammatory response

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

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